Department of Laboratory Medicine, Division of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
Institute of Hygiene, University of Münster, Münster, Germany.
Nat Biotechnol. 2021 Jun;39(6):754-764. doi: 10.1038/s41587-020-00805-3. Epub 2021 Feb 11.
Is the oncogene MYC upregulated or hyperactive? In the majority of human cancers, finding agents that target c-MYC has proved difficult. Here we report specific bacterial effector molecules that inhibit cellular MYC (c-MYC) in human cells. We show that uropathogenic Escherichia coli (UPEC) degrade the c-MYC protein and attenuate MYC expression in both human cells and animal tissues. c-MYC protein was rapidly degraded by both cell-free bacterial lysates and the purified bacterial protease Lon. In mice, intravesical or peroral delivery of Lon protease delayed tumor progression and increased survival in MYC-dependent bladder and colon cancer models, respectively. These results suggest that bacteria have evolved strategies to control c-MYC tissue levels in the host and that the Lon protease shows promise for therapeutic targeting of c-MYC in cancer.
癌基因 MYC 是否上调或过度活跃？在大多数人类癌症中，发现针对 c-MYC 的药物证明很困难。在这里，我们报告了专门的细菌效应分子，可抑制人细胞中的细胞 MYC（c-MYC）。我们表明，尿路致病性大肠杆菌（UPEC）降解 c-MYC 蛋白，并减弱人细胞和动物组织中的 MYC 表达。无细胞细菌裂解物和纯化的细菌蛋白酶 Lon 均可快速降解 c-MYC 蛋白。在小鼠中，膀胱内或口服给予 Lon 蛋白酶分别延迟了依赖 MYC 的膀胱癌和结肠癌模型中的肿瘤进展并提高了存活率。这些结果表明，细菌已经进化出在宿主中控制 c-MYC 组织水平的策略，而 Lon 蛋白酶有望成为癌症中 c-MYC 的治疗靶标。
